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DRUG INTERACTIONS Drug Interactions:
Itraconazole and its major metabolite, hydroxyitraconazole, are inhibitors of CYP3A4. Therefore, the following drug interactions may occur
(See Table 1 below and the following drug class subheadings that follow):
- SPORANOX® may decrease the elimination of drugs metabolized by CYP3A4, resulting in increased plasma concentrations of these drugs when they are administered with SPORANOX®. These elevated plasma concentrations may increase or prolong both therapeutic and adverse effects of these drugs. Whenever possible, plasma concentrations of these drugs should be monitored, and dosage adjustments made after concomitant SPORANOX® therapy is initiated. When appropriate, clinical monitoring for signs or symptoms of increased or prolonged pharmacologic effects is advised. Upon discontinuation, depending on the dose and duration of treatment, itraconazole plasma concentrations decline gradually (especially in patients with hepatic cirrhosis or in those receiving CYP3A4 inhibitors). This is particularly important when initiating therapy with drugs whose metabolism is affected by itraconazole.
- Inducers of CYP3A4 may decrease the plasma concentrations of itraconazole. SPORANOX® may not be effective in patients concomitantly taking SPORANOX® and one of these drugs. Therefore, administration of these drugs with SPORANOX® is not recommended.
- Other inhibitors of CYP3A4 may increase the plasma concentrations of itraconazole. Patients who must take SPORANOX® concomitantly with one of these drugs should be monitored closely for signs or symptoms of increased or prolonged pharmacologic effects of SPORANOX®.
Table 1. Selected Drugs that are predicted to alter the plasma concentration of itraconazole or have their plasma concentration altered by SPORANOX® This list is not all-inclusive. | Drug plasma concentration increased by itraconazole |
| Antiarrhythmics | digoxin, dofetilide , quinidine, disopyramide |
| Anticonvulsants | carbamazepine |
| Antimycobacterials | rifabutin |
| Antineoplastics | busulfan, docetaxel, vinca alkaloids |
| Antipsychotics | pimozide |
| Benzodiazepines | alprazolam, diazepam, midazolam, ,
triazolam |
| Calcium Channel Blockers | dihydropyridines (including nisoldipine), verapamil |
| Gastrointestinal Motility Agents | cisapride |
| HMG CoA-Reductase Inhibitors | atorvastatin, cerivastatin, lovastatin, simvastatin |
| Immunosuppressants | cyclosporine, tacrolimus, sirolimus |
| Oral Hypoglycemics | oral hypoglycemics |
| Protease Inhibitors | indinavir, ritonavir, saquinavir |
| Other | levacetylmethadol (levomethadyl), ergot alkaloids, halofantrine, alfentanil, buspirone, methylprednisolone, budesonide, dexamethasone, fluticasone, trimetrexate, warfarin, cilostazol, eletriptan, fentanyl |
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| Decrease plasma concentration of itraconazole |
| Anticonvulsants | carbamazepine, phenobarbital, phenytoin |
| Antimycobacterials | isoniazid, rifabutin, rifampin |
| Gastric Acid Suppressors/Neutralizers | antacids, H2-receptor antagonists, proton pump inhibitors |
| Non-nucleoside Reverse Transcriptase Inhibitors | nevirapine |
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| Increase plasma concentration of itraconazole |
| Macrolide Antibiotics | clarithromycin, erythromycin |
| Protease Inhibitors | indinavir, ritonavir |
Antiarrhythmics:
The class IA antiarrhythmic quinidine and class III antiarrhythmic dofetilide are known to prolong the QT interval. Coadministration of quinidine or dofetilide with SPORANOX® may increase plasma concentrations of quinidine or dofetilide which could result in serious cardiovascular events. Therefore, concomitant administration of SPORANOX® and quinidine or dofetilide is contraindicated. (See BOX WARNING, CONTRAINDICATIONS, and WARNINGS.)
The class IA antiarrhythmic disopyramide has the potential to increase the QT interval at high plasma concentrations. Caution is advised when SPORANOX® and disopyramide are administered concomitantly.
Concomitant administration of digoxin and SPORANOX® has led to increased plasma concentrations of digoxin.
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OVERDOSAGE
Itraconazole is not removed by dialysis. In the event of accidental overdosage, supportive measures, including gastric lavage with sodium bicarbonate, should be employed.
Limited data exist on the outcomes of patients ingesting high doses of itraconazole. In patients taking either 1000 mg of SPORANOX® (itraconazole) Oral Solution or up to 3000 mg of SPORANOX® (itraconazole) Capsules, the adverse event profile was similar to that observed at recommended doses.
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CONTRAINDICATIONS
Congestive Heart Failure:
SPORANOX® (itraconazole) Capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF. (See CLINICAL PHARMACOLOGY: Special Populations, WARNINGS, PRECAUTIONS: Drug Interactions-Calcium Channel Blockers, and ADVERSE REACTIONS: Post-marketing Experience.)
Drug Interactions:
Concomitant administration of SPORANOX® (itraconazole) Capsules, Injection, or Oral Solution and certain drugs metabolized by the cytochrome P450 3A4 isoenzyme system (CYP3A4) may result in increased plasma concentrations of those drugs, leading to potentially serious and/or life-threatening adverse events. Cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide, triazolam and levacetylmethadol (levomethadyl) are contraindicated with SPORANOX®. HMG CoA-reductase inhibitors metabolized by CYP3A4, such as lovastatin and simvastatin, are also contraindicated with SPORANOX®. Ergot alkaloids metabolized by CYP3A4 such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine) are contraindicated with SPORANOX®. (See BOX WARNING, and PRECAUTIONS: Drug Interactions.)
SPORANOX® should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy.
SPORANOX® is contraindicated for patients who have shown hypersensitivity to itraconazole or its excipients. There is no information regarding cross-hypersensitivity between itraconazole and other azole antifungal agents. Caution should be used when prescribing SPORANOX® to patients with hypersensitivity to other azoles.
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Page last updated: 2008-01-24
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